What diagnostic tests should be ordered on ascitic fluid to determine the cause of ascites?

Diagnostic Testing for Ascitic Fluid

Every patient with new-onset ascites or hospitalized cirrhotic patients with ascites must undergo diagnostic paracentesis with a core panel: cell count with differential, ascitic fluid albumin plus simultaneous serum albumin to calculate SAAG, total protein, and bedside inoculation of ≥10 mL into blood culture bottles before any antibiotics are given. 1, 2

Mandatory Initial Tests (Order on Every Paracentesis)

Cell Count with Differential

• An ascitic fluid neutrophil count ≥250 cells/mm³ defines spontaneous bacterial peritonitis (SBP) and requires immediate empirical antibiotic therapy without waiting for culture results. 1, 2
• SBP is present in approximately 15% of cirrhotic patients with ascites at hospital admission. 1, 2
• Automated cell counting methods provide accurate results and are acceptable alternatives to manual microscopy. 2

Serum-Ascites Albumin Gradient (SAAG)

• Measure ascitic fluid albumin and serum albumin on the same day; subtract ascitic albumin from serum albumin to calculate SAAG. 1, 2
• SAAG ≥1.1 g/dL indicates portal hypertension with 97% diagnostic accuracy. 1, 2, 3, 4
• SAAG <1.1 g/dL suggests non-portal hypertensive causes: malignancy, tuberculosis, nephrotic syndrome, or pancreatic disease. 1, 2
• SAAG has superseded the older exudate/transudate classification system. 2

Total Protein

• Ascitic fluid total protein <1.5 g/dL identifies patients at high risk for developing SBP and guides prophylactic antibiotic decisions. 1, 2

Bacterial Culture

• Inoculate ≥10 mL of ascitic fluid into blood culture bottles at the bedside before any antibiotics are administered. 1, 2
• Bedside inoculation increases culture yield from ~50% to 80-90%. 2
• Blood cultures should also be obtained in all patients with suspected SBP. 1

Targeted Additional Tests (Order Only When Clinically Indicated)

When Secondary Bacterial Peritonitis is Suspected

• Order ascitic fluid glucose, lactate dehydrogenase (LDH), and Gram stain. 1, 2
• Glucose <50 mg/dL, LDH higher than serum LDH, or multiple organisms on Gram stain indicate bowel perforation requiring surgical evaluation. 1, 2
• Ascitic fluid carcinoembryonic antigen >5 ng/mL or alkaline phosphatase >240 U/L supports gastrointestinal perforation. 2

When Malignant Ascites is Suspected (SAAG <1.1 g/dL)

• Order cytology only when peritoneal carcinomatosis is clinically suspected (e.g., known breast, colon, gastric, or pancreatic cancer). 2
• Sensitivity is 96.7% when three fresh 50-mL samples are processed; first sample alone is positive in 82.8%. 2
• Do not order CA-125 because it is elevated in virtually all ascites types and lacks diagnostic specificity. 2

When Tuberculous Peritonitis is Suspected

• Order adenosine deaminase (ADA) testing in patients from endemic regions or with HIV infection. 1, 2
• Ascitic fluid smear for mycobacteria has ~0% sensitivity; culture sensitivity is ~50%. 1
• Laparoscopy with biopsy and mycobacterial culture of tubercles provides the most rapid and accurate diagnosis. 1

When Pancreatic Ascites is Suspected

• Order ascitic amylase when there is clinical suspicion of pancreatic disease. 1
• Ascitic amylase >1,000 U/L or >6 times serum amylase supports pancreatic origin. 2

When Cardiac Ascites is Suspected

• Measure serum BNP or NT-proBNP to distinguish heart failure from cirrhosis. 2
• Median pro-BNP values are ~6,100 pg/mL in heart failure versus ~166 pg/mL in cirrhosis. 2
• Examine for jugular venous distension to further differentiate alcoholic cardiomyopathy from alcoholic cirrhosis. 2

When Chylous Ascites is Suspected (Milky White Fluid)

• Order ascitic fluid triglyceride level; >200 mg/dL confirms the diagnosis. 5
• Triglyceride levels often exceed 1,000 mg/dL in true chylous ascites. 5

Indications for Diagnostic Paracentesis

• All patients with new-onset ascites at first presentation, regardless of symptoms. 1, 2
• Every hospitalized cirrhotic patient with ascites on admission, even if asymptomatic. 1, 2
• Any cirrhotic patient with ascites who develops fever (≥38°C), abdominal pain, encephalopathy, rising creatinine, gastrointestinal bleeding, shock, metabolic acidosis, or unexplained peripheral leukocytosis. 1, 2

Safety Considerations

• Paracentesis can be safely performed despite coagulopathy (INR up to 8.7, platelets as low as 19×10³/µL); major complications occur in only ~1% of procedures. 2
• Routine prophylactic correction with fresh-frozen plasma or platelets is not recommended. 1, 2
• The only absolute contraindications are clinically evident disseminated intravascular coagulation or active fibrinolysis, occurring in <1 per 1,000 procedures. 2

Common Pitfalls to Avoid

• Do not order a battery of tests on every ascitic fluid specimen—use an algorithmic approach where initial results (SAAG, neutrophil count, total protein) guide further testing. 6, 7
• Do not withhold paracentesis because of abnormal coagulation parameters; bleeding risk is minimal. 2
• Do not order CA-125 for ascites evaluation; it lacks specificity. 2
• Do not rely solely on fluid appearance to diagnose chylous ascites; confirm with triglyceride measurement. 5